Shachar Sade

Major psychological complications and decreased health-related quality of life among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis

DEAR EDITOR, Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous reactions, predominantly drug induced. No studies have been conducted on the psychological sequelae or general healthrelated quality of life (HRQOL) among survivors of SJS/TEN. Two studies that explored patients’ perspectives of surviving SJS/TEN found a persisting impact on survivors’ current lives physically and psychologically, as well as many unanswered questions and concerns. Survivors of burns were found to be at risk of post-traumatic stress disorder (PTSD) and other psychological sequelae including depression and anxiety. Recent work on drug reaction with eosinophilia and systemic symptoms found that survivors experience anxiety, depression, nightmares and intrusive thoughts. In this study we characterize the long-term psychological complications and HRQOL of SJS/TEN survivors. The study was approved by the research ethics board at Sunnybrook Health Sciences Centre. All participants provided informed consent prior to study inclusion. The cohort included survivors of SJS/TEN treated at Sunnybrook Health Sciences Centre, Toronto, Canada during 1995–2015. Inclusion criteria included biopsy-proven diagnosis of SJS/TEN and age > 18 years. Exclusion criteria included any medical condition that would disqualify the patient from answering questionnaires. Patients were enrolled in the study from 15 July 2014 to 25 March 2015. Participants were assessed by psychological and HRQOL questionnaires. We chose psychometric, validated scales that would capture symptoms of depression and anxiety in a medical context (Hospital Anxiety and Depression Scale), overall psychological distress (General Health Questionnaire12, GHQ-12) and evidence of PTSD (Impact of Events Scale-Revised). HRQOL was assessed by three validated questionnaires – Dermatology Life Quality Index, Skindex-29 and EQ-5D – and one specially designed for this study: SJS/TEN Survivors HRQOL (Appendix S1; see Supporting Information). The participants were also assessed by a medical interview. Descriptive statistics were calculated for variables of interest. Continuous variables were reported using means and SDs, whereas categorical variables were reported using counts and percentages. Fisher’s exact test and the Wilcoxon rank sum test were used to measure associations (P < 0 05). Statistical analyses were carried out with SAS version 9.3 (SAS Institute Inc., Cary, NC, U.S.A.) and SPSS (IBM, Armonk, NY, U.S.A.). We identified 44 survivors to whom we sent introductory letters about the study. We reached 21 survivors by telephone; three refused to participate in the study and one had dementia and therefore was not included. Our cohort included 17 patients (11 female and six male) with a mean 51 6 74 7 months (median 9, range 1–228) following hospital discharge due to SJS/TEN. The patients’ characteristics are summarized in Table 1. The results of the psychological and HRQOL questionnaires are summarized in Table 2. We would like to highlight the important findings: 65% of participants had symptoms of post-traumatic stress and 29% even had total scores in keeping with clinical signs of possible PTSD. Seventy-one percent of participants had scores indicating clinically significant psychological distress. Four participants had a past psychiatric disorder, but there was no statistically significant association with scores in the psychological assessment questionnaires (P < 0 05). Surviving SJS/TEN was found

Syringoid eccrine carcinoma: a clinicopathological and immunohistochemical study of four cases

Background Syringoid eccrine carcinoma (SEC) is a rare malignant adnexal tumour with variable presentations. Aim To examine the clinicopathological and immunohistochemical features of SEC. Methods Four cases were reviewed by three dermatopathologists and the immunohistochemical profile was examined using antibodies against CK5/6, CK7, CK14, CK20, LMWK, HMWK, EMA, mCEA, p63, ER, PR, AR, S-100 and Ber-EP4. Results The cases occurred in two men and two women, ranging in age from 61 to 87 years (mean 68.5). Two of the lesions were from the face and two from the trunk. All four lesions were composed of an atypical infiltrative mass with syringoma-like tadpole morphology with ductular differentiation and prominent desmoplasia. Three cases demonstrated perineural invasion and two had positive lymph node metastases. Immunostaining was variable. Immunohistochemistry positivity was as follows: three out of four cases were positive for CK5/6, CK7 (2/4), CK14 (1/3), CK20 (0/2), HMWK (0/2), LMWK (1/2), EMA (3/4), mCEA (4/4), p63 (2/3), ER (2/3), PR (1/2), AR (0/3), S-100 (0/3) and Ber-EP4 (2/2). Conclusion SEC can present on the trunk and are not limited to the head and neck region. In addition to syringoma-like tadpole structures and glandular differentiation, these tumours can also exhibit squamoid and cribriform growth patterns. Immunostaining in SEC is variable and this variability is believed to stem from this tumours ability to differentiate along multiple routes, including sweat secretory and/or ductal differentiation.

Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model

BackgroundMost cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients’ quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model.MethodsAthymic mice were treated intraperitoneally with saline or Vasculotide and their flank skin was irradiated with a single large dose of ionizing radiation. Acute cutaneous damage and wound healing were evaluated by clinical skin grading, histology and immunostaining. Diffuse reflectance optical spectroscopy, myeloperoxidase-dependent bioluminescence imaging of neutrophils and a serum cytokine array were used to assess inflammation. Microvascular endothelial cell response to radiation was tested with in vitro clonogenic and Matrigel tubule formation assays. Tumour xenograft growth delay experiments were also performed. Appreciable differences between treatment groups were assessed mainly using parametric and non-parametric statistical tests comparing areas under curves, followed by post-hoc comparisons.ResultsIn vivo, different schedules of Vasculotide treatment reduced the size of the irradiation-induced wound. Although skin damage scores remained similar on individual days, Vasculotide administered post irradiation resulted in less skin damage overall. Vasculotide alleviated irradiation-induced inflammation in the form of reduced levels of oxygenated hemoglobin, myeloperoxidase bioluminescence and chemokine MIP-2. Surprisingly, Vasculotide-treated animals also had higher microvascular endothelial cell density in wound granulation tissue. In vitro, Vasculotide enhanced the survival and function of irradiated endothelial cells.ConclusionsVasculotide administration reduces acute skin radiation damage in mice, and may do so by affecting several biological processes. This radiation protection approach may have clinical impact for cancer radiotherapy patients by reducing the severity of their acute skin radiation damage.

Pyoderma gangrenosum secondary to azacitidine in myelodysplastic syndrome.

A 66-year-old female was diagnosed with myelodysplastic syndrome (MDS), specifically refractory cytopenia with multilineage dysplasia. Her bone marrow demonstrated 3% blasts with a complex karyotype and she had transfusion-dependent anaemia and thrombocytopenia. She was started on azacitidine for very high-risk MDS, as determined by her Revised International Prognostic Scoring System score. The first cycle of azacitidine was well tolerated. Three days into her second cycle, multiple erythematous, painful pustular plaques with a violaceous border and central haemorrhagic crusting appeared on her lips, inner nose and upper arms (top). Empirical ciprofloxacin and clindamycin had no clinical benefit and the lesions then progressed to involve her forearms, with three dominant lesions 3–4 cm in diameter. A skin biopsy demonstrated a neutrophilic infiltrate with marked acute inflammation and reactive changes (bottom); microbiological studies were negative. The clinical and pathological presentation was in keeping with pyoderma gangrenosum (PG). She was treated with prednisone and colchicine, and the azacitidine was withheld for 2 months with subsequent healing of the lesions. The forearm lesions recurred when re-challenged with azacitidine, but promptly responded to a second course of prednisone. Neutrophilic dermatoses, including Sweet syndrome and PG, are uncommon but well-documented dermatological sequalae of MDS. However, given the recurrence of skin lesions with therapy, the clinical and pathological picture was most in keeping with PG secondary to azacitidine, rather than to the underlying disease. PG in MDS has also been linked to the administration of granulocyte colony-stimulating factor. While our patient’s skin lesions were controlled with concurrent colchicine and corticosteroids, her MDS did not improve with azacitidine and as a result, this drug was stopped after five cycles. Eric Tseng, Raed Alhusayen, Shachar Sade, Rena Buckstein and Anca Prica Sunnybrook Health Sciences Centre, University of Toronto, and Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. E-mail: anca.prica@uhn.ca images in haematology

Syringocystadenocarcinoma papilliferum in situ of the penis

ejd.2012.1723 Auteur(s) : Mathew A. Plant1, Shachar Sade2, Collin Hong3, Danny MD Ghazarian4 Danny.Ghazarian@uhn.on.ca 1 Department of Surgery, Toronto General Hospital, 2 Department of Pathology Sunnybrook Health Sciences Centre, Toronto, Canada 3 Cosmetic, Plastic and Reconstructive Surgeon, Toronto, Canada 4 Department of Pathology, Toronto General Hospital, 190 Elizabeth St, Toronto, M5G 2C4, Canada Syringocystadenocarcinoma papilliferum (SCACP) is the malignant version of syringocystadenoma [...]

Spindle cell melanocytic lesions: part II—an approach to intradermal proliferations and horizontally oriented lesions

Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes show a dendritic cytomorphology and territorial isolation, lesional nevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies, and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may either be a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either due to its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion due to a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified; however, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions may reliably be resolved through this standard approach, problem areas do exist for the surgical pathologist or dermatopathologist. With this review (part II of II), we complete our discussion of spindle cell melanocytic lesions, in order to: (1) model a systematic approach to such lesions; and (2) provide familiarity with those melanocytic lesions which either typically or occasionally display a spindled cytomorphology.

Spindle cell melanocytic lesions--part I: an approach to compound naevoidal pattern lesions with spindle cell morphology and Spitzoid pattern lesions.

Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes reveal a dendritic cytomorphology and territorial isolation, lesional naevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may be either a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either because of its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion because of a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified. However, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions can reliably be resolved with this standard approach, problem areas do exist and cause no end of grief to the surgical pathologist or dermatopathologist. In this review, the authors present their algorithmic approach to spindle cell melanocytic lesions and discuss each entity in turn, in order to (1) model a systematic approach to such lesions, and (2) provide familiarity with those melanocytic lesions that either typically or occasionally display a spindled cytomorphology.

Pathologic Complete Response to Intralesional Interleukin-2 Therapy Associated with Improved Survival in Melanoma Patients with In-Transit Disease

Purpose Melanoma patients with in-transit disease have a high mortality rate despite various treatment strategies. The aim of this study was to validate the role of intralesional interleukin (IL)-2, to understand its mechanism of action, and to better understand factors that may influence its response.

From the outside looking in.

Yasbanoo Moayedi, MD, Paul E. Bunce, MD, Shachar Sade, MD, Danny Ghazarian, MD, Wayne L. Gold, MD Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Infectious Diseases, Department of Medicine, niversity Health Network, Toronto, Ontario, Canada; Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, ntario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology, University Health Network, Toronto, Ontario, Canada.